, Volume 54, Issue 3, pp 620–633 | Cite as

Antigen-based immunotherapies do not prevent progression of recent-onset autoimmune diabetes: a systematic review and meta-analysis

  • Chrysoula Rizava
  • Eleni Bekiari
  • Aris Liakos
  • Maria Sarigianni
  • Maria Rika
  • Anna Bettina Haidich
  • Asimina Galli-Tsinopoulou
  • Apostolos Tsapas


We performed a systematic review and meta-analysis to assess the efficacy and safety of antigen-based immunotherapies in tertiary prevention of autoimmune diabetes. We searched for randomised controlled trials testing antigen-based immunotherapies in patients with recent-onset type 1 diabetes or latent autoimmune diabetes of adults in MEDLINE, COCHRANE and EMBASE databases, trial registries, conference proceedings and reference lists of pertinent records. Primary outcomes were fasting and stimulated C-peptide (after glucagon or mixed meal stimulation). Change in glycosylated haemoglobin (HbA1c), daily insulin needs and incidence of any or severe hypoglycaemic events or severe adverse events were secondary outcomes. Fifteen studies were included in the meta-analysis. Overall, there was no difference in fasting [weighted mean difference (WMD) 0.01 nmol/L; 95 % confidence interval (CI) −0.09, 0.11; I 2 = 73 %] or mixed meal stimulated C-peptide (WMD 0.02 nmol/L/min; 95 % CI −0.08, 0.12; I 2 = 50 %) compared with placebo. Glucagon stimulated C-peptide was maintained higher (WMD 0.13 nmol/L/min; 95 % CI 0.05, 0.21; I 2 = 0 %) in patients treated with Diapep277. Moreover, there was no change in daily insulin needs (WMD 0.02 IU/kg; 95 % CI −0.04, 0.09; I 2 = 51 %) or HbA1c (WMD −0.06 %; 95 % CI −0.35, 0.23; I 2 = 42 %) vs. placebo. Finally, there was no effect on the incidence of severe hypoglycaemic events or overall serious adverse events [risk ratio 0.94, 95 % CI 0.62, 1.41; I 2 = 0 % and 0.87; 95 % CI 0.53, 1.44; I 2 = 0 %, respectively). Antigen-based immunotherapies are not effective in preventing the progression of autoimmune diabetes in newly diagnosed patients.


Diabetes, Autoimmune Immunotherapy Tertiary prevention Insulin Glutamate decarboxylase Chaperonin 60 



CR and AT conceived the study. CR, AGT and AT designed the study. CR and EB searched the scientific literature. CR and MR did data extraction. CR and MS did risk of bias assessment and grading of recommendations. CR and AL conducted the statistical analysis and ABH contributed to the analysis. CR, AL and AT drafted the paper. EB, MR and AGT contributed to the interpretation of the findings. All authors edited and approved the final version of the manuscript to be published. AT had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary information


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Chrysoula Rizava
    • 1
  • Eleni Bekiari
    • 1
    • 2
  • Aris Liakos
    • 1
  • Maria Sarigianni
    • 1
  • Maria Rika
    • 2
  • Anna Bettina Haidich
    • 3
  • Asimina Galli-Tsinopoulou
    • 4
  • Apostolos Tsapas
    • 1
    • 2
    • 5
  1. 1.Clinical Research and Evidence-Based Medicine UnitAristotle University ThessalonikiThessalonikiGreece
  2. 2.Diabetes Centre, Second Medical DepartmentAristotle University ThessalonikiThessalonikiGreece
  3. 3.Department of Hygiene and Epidemiology, School of Health Sciences, Department of MedicineAristotle University ThessalonikiThessalonikiGreece
  4. 4.Fourth Paediatric DepartmentAristotle University ThessalonikiThessalonikiGreece
  5. 5.Harris Manchester CollegeUniversity of OxfordOxfordUK

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